Benefits of Patisiran on Functional Capacity in ATTR Cardiac Amyloidosis

Abstract

Background

Patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) suffer substantial morbidity and mortality. The meaningful preservation of functional capacity and quality of life are important priorities.

Objectives

The 6-minute walk test (6MWT), a measure of functional capacity, was the primary outcome in the APOLLO-B study of patisiran in patients with ATTR-CM; the treatment benefit vs placebo was +15 m over 12 months. We estimated the minimal clinically important difference for change in 6MWT performance.

Methods

Change from baseline in 6MWT performance was anchored to established categories of clinically important change in the Kansas City Cardiomyopathy Questionnaire-Overall Summary score. To relate changes in 6MWT performance to activities of daily living, we fit a proportional-odds cumulative logit model for items in the Kansas City Cardiomyopathy Questionnaire Physical Limitation domain.

Results

The APOLLO-B trial randomized 360 patients to receive placebo (n = 179) or patisiran (n = 181). The estimated minimal clinically important difference in 6MWT was 6.9 to 7.8 m. When comparing the change from baseline in 6MWT at month 12 between 2 patients, 15 m greater preservation was associated with approximately 10% to 16% lower odds of deterioration in walking 1 block (OR: 0.88 [95% CI: 0.83-0.93]), climbing stairs (OR: 0.84 [95% CI: 0.80-0.89]), hurrying/jogging (OR: 0.88 [95% CI: 0.83-0.93]), dressing oneself (OR: 0.85 [95% CI: 0.81-0.90]), and performing yard/housework or carrying groceries (OR: 0.89 [95% CI: 0.84-0.93]).

Conclusions

In patients with ATTR-CM treated with patisiran, mean population-level differences of 7 to 8 m in 6MWT have practical relevance. The magnitude of the impact of patisiran on 6MWT performance over 12 months in APOLLO-B was associated with preserving the ability to perform activities of daily living.